. Regulation of cell cycle depends on the scheduled expression of a class of proteins termed cyclins, and the interaction of these proteins with cyclin-dependent kinases (Cdk) and cyclin-dependent kinase-inhibitor (Cki) proteins. Derangement in cell cycle regulatory proteins clearly contributes to the uncontrolled cell growth that is characteristic of cancer. Thus, these proteins are implicated as causal factors in the development of cancer. Information from several studies, support the hypothesis that altered expression of a G1 phase cyclin, Cyclin E, is a common and highly relevant occurrence in breast cancer. Preliminary studies indicate that Cyclin E is aberrantly expressed in breast cancer tissue: 1) it is present at higher levels in cancer cells than benign cells in the same patient; 2) in some tumors, it appears to be independent of proliferation; and 3) high levels of expression are associated with tumors of higher grade and poor prognosis. The plan is to test tumors from women enrolled in the ongoing study, "Factors That Affect Survival of Young Cancer Patients," and evaluate Cyclin E and the cell cycle inhibitors (p27 and p21) expression in invasive breast cancer specimens, using immunocytochemical and flow cytometric assays. The results are expected to be combined with the extensive epidemiological, clinical, and histopathological, tumor marker, and flow cytometric cell cycle data currently being collected as part of the larger study. The data are expected to provide important new information of the cyclins in the development of breast cancer and, in this large population, will allow determination of whether alterations of Cyclin E and cell cycle inhibitor protein expression are predictors of recurrence or death in breast cancer.